Malignant transformation is accompanied by extensive alterations in the cell surface mosaic. This project will employ immunochemical techniques to study spatial and temporal aspects of surface antigen expression during chemically induced hepatocarcinogenesis in rats. Monoclonal antibodies will be prepared to relevant tissue-specific, stage-specific, tumor-associated and differentiation antigens of normal adult and fetal hepatocytes, regenerating liver cells, oval cells and transplantable hepatocellular carcinoma cells. The reactive antigens will be isolated and characterized. Immunocytochemical techniques will be used to examine the livers of rats undergoing carcinogenesis for alterations in expression of the relevant antigens, and the sera of rats exposed to hepatocarcinogens will be examined for the presence of antigenic markers. In order to determine the relationship of tumor-associated antigens to transforming genes, BALB/3T3 cells will be transfected with DNA isolated from rat transplantable carcinomas and examined for expression of rat tumor-associated antigens. These studies will contribute to our understanding of the molecular basis of cell surface alterations which accompany malignant transformation and provide insight into the mechanism of carcinogenesis.